Total synthesis of indole and dihydroindole alkaloids. VI. The total synthesis of some monomeric vinca alkaloids: dl-vincadine, dl-vincaminoreine, dl-vincaminorine, dl-vincadifformine, dl-minovine and dl-vincaminoridine.

A synthetic approach to a variety of monomeric Vinca alkaloids is described. The sequence involves, among its crucial phases, the generation of appropriate nine-membered ring intermediates which are then elaborated via a transannular cyclization approach to the desired natural products.     

Total synthesis of indole and dihydroindole alkaloids. IX. Studies on the synthesis of bisindole alkaloids in the vinblastine-vincristine series. The biogenetic approach.

A detailed study of the reaction of catharanthine N-oxide and vindoline has been carried out employing various conditions. Under optimum conditions, which involve low temperatures and trifluoroacetic anhydride as reagent, 3′, 4′-dehydrovinblastine (XIII, R = COOCH₃), in reasonable yields is essentially the exclusive product. However two additional products, 18′ (epi)- 3′, 4′-dehydrovinblastine (XIV, R = COOCH₃) and 1′-hydroxy- 3′, 4′-dehydrovinblastine (XVI, R = COOCH₃) are also often isolated. The reaction, which follows the course of a Polonovski-type fragmentation process, has been extended to the N-oxide derivatives of dihydrocatharanthine and decarbomethoxycatharanthine to provide again a series of bisindole alkaloid derivatives, also vinblastines. A mechanistic rationale is provided to explain the various results obtained.     

Total synthesis of indole and dihydroindole alkaloids. VIII. Studies on the synthesis of bisindole alkaloids in the vinblastine-vincristine series. The chloroindolenine approach.

Studies on the syntheses of 18′-epi-4′-deoxo-4′-epivinblastine (IX, R = CO₂CH₃; R₁ = H), 18′-decarbomethoxy-18′-epi-4′-deoxo-4′-epivinblastine (IX, R = R₁ = H) and related analogues are described. The synthetic method employs a coupling reaction involving chloroindolenine derivatives of the cleavamine series (for example, III) with vindoline (V) under acidic conditions. The complete structures, including absolute configuration, of the resulting dimers are established by a combination of chemical and spectroscopic techniques, including X-ray analysis.     

Total synthesis of the indole alkaloids ngouniensine and epingouniensine

The first total synthesis of ngouniensine and epingouniensine, by cyclization of a suitable 1-(3-indolylethyl)piperidine-2-carboxylic acid followed by the elaboration of the exocyclic methylene group, is reported.     

Tremorgenic indole alkaloids. The total synthesis of (-)-penitrem D

A convergent, stereocontrolled total synthesis of the architecturally complex tremorgenic indole alkaloid (-)-penitrem D (4) has been achieved. Highlights of the synthesis include an efficient, asymmetric synthesis of the western hemisphere; the stereocontrolled assembly of the I-ring; discovery of a novel autoxidation to introduce the C(22) tertiary hydroxyl group, required for tremorgenic activity; union of fully elaborated eastern and western hemispheres, exploiting an indole synthetic protocol developed expressly for this purpose; and a late-stage, stereoselective construction of the A and F rings exploiting a Sc(OTf)(3-)promoted reaction cascade. The longest linear sequence leading to (-)-penitrem D (4) was 43 steps.     

Total synthesis of the indole alkaloids henrycinol A and B

The total synthesis of new indole alkaloids henrycinol A and B were accomplished starting from l-tryptophan methyl ester. The key step is a stereochemically flexible Pictet–Spengler reaction governed by the presence or absence of an N-allyl group in the tryptophan precursor. The natural products henrycinol A and B were synthesized in good overall yield in eight and nine steps, respectively.     

Total synthesis of the proposed structures of indole alkaloids lyaline and lyadine

The harman-1,4-dihydropyridines 1 and 2, which constitute the originally proposed structures for the indole alkaloids lyaline and lyadine, have been synthesized, and their NMR data have been compared with those available for the natural products. Due to the discrepancies in the spectral data, the structures of lyadine and lyaline should be revised.     

Transfer of functionalized carbon fragments via substituted 5, 10-methylentetetrahydrofolate models. : Approach to dihydroindole and indole alkaloids.

4-(2-N(1)-tosyl-N(3)-methyl-4-,4-dimethylimidazolidyl)-3-ketobutanoate reacts with tryptamine, in the presence of acetic acid, to give primary “carbon transfer” products, which can be conveniently converted to synthetically useful indole and dihydroindole derivatives.     

An asymmetric synthesis of indole alkaloids

Chiral formamidines derived from β-carbolines are metallated and alkylated stereoselectively opening a route to indole alkaloids and analogous compounds.     

Total synthesis of marine sponge bis(indole) alkaloids of the topsentin class

The synthesis of four natural bis(indole) alkaloids of topsentin class 1 and 2 is described. Their bis(indole) alpha-carbonylimidazoline and subsequently bis(indole) alpha-carbonylimidazole moieties have been built via the condensation between indolic alpha-ketothioimidate salts 4 and 1-(indol-3'-yl)-1,2-diaminoethane 3. This compound results from the beta-amino indolic hydroxylamine 5 by a two-step sequence. This is the first total synthesis of compounds 1d, 2a, and 2b.     

Fluorous and traceless synthesis of substituted indole alkaloids

The fluorous traceless synthesis of substituted indole alkaloids is carried out first by attaching the 3-(perfluorooctyl)propanol with Boc protected L-tryptophan. The reaction of perfluoroalkyl (Rfh)-tagged tryptophan esters with various aldehydes undergoes Pictet-Spengler reaction to give cis and trans stereoisomers of tetrahydro-beta-carbolines. The nucleophilic addition of the piperidine nitrogen across various isocyanates is followed by the cyclization of ureas and simultaneous rupture of the fluorous tag to afford the hydantoin ring fused tetrahydro-beta-carbolines. All the fluorous-tag compounds are purified by solid-phase extraction (SPE) through Fluoro Flash cartridges.